Cell Membrane-mimetic Iron-silicon Nanoparticles For Enhanced Sonodynamic Cancer Therapy

Ultrasound（US）-triggered sonodynamic therapy（SDT）has attracted significant attention in latest years.Nevertheless,the therapeutic efficacy is compromised by insufficient target of sonosensitizers and intra-tumor transport barriers.Herein,a cancer cell membrane（CCM）functionalized iron-silicon nanoparticles（MSF@CCM）was constructed to achieve efficient tumor therapy with the assistance of US.The functionalized of CCM not only confers the homologous targeting ability of MSF,but also effectively circumvents clearance by the macrophage system,which facilitates efficient accumulation of MSF@CCM in tumor tissues.Meanwhile,the US-mediated sonoporation effect can transiently open blood vessels,allowing MSF@CCM to penetrate more effectively from outside the vasculature to deeper into the tumor.Furthermore,MSF@CCM can efficiently generate reactive oxygen species（ROS）under US irradiation and exhibits better sonodynamic properties compared to Fe OOH nanodots.More importantly,MSF@CCM has the ability to deplete glutathione and catabolize H₂O₂,which could further enhance ROS production within the tumor microenvironment.Ultimately,the potent anti-tumor effects of MSF@CCM in combination with US were validated in vitro and in a 4T1tumor-bearing mouse model.It is believed that biomimetic construction strategy provides a promising therapeutic modality for enhancing active targeting of sonosensitizers and overcoming intra-tumor transport barriers to achieve efficient SDT.